Articles: neuralgia.
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The research of new therapeutic strategies for neuropathic pain represents a major current priority. Important drawbacks to advance in the development of these therapies are the limited translational value of the animal models now available and the elucidation of the complex neuronal and immune pathophysiological mechanisms underlying neuropathic pain. One of the neurotransmitter systems participating in neuropathic pain control that has recently raised a particular interest is the endocannabinoid system. ⋯ Several clinical studies suggest that cannabinoids significantly reduced neuropathic pain, although most of these trials fail the required standards of quality. The different pain patient populations included in the systematic reviews also make it difficult to get adequate conclusions. Therefore, additional clinical trials that consider an adequate number of patients, the use active treatments as controls, and longer duration of administration are required to have an adequate profile of the effectiveness and safety of cannabinoids in neuropathic pain.
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Pulsed radiofrequency (PRF) is a novel nondestructive interventional technique for the treatment of neuropathic pain (NP). However, this intervention is still lack of relevant regulation and the mechanism of action is insofar not clear. Historically, most studies have reported that PRF can relieve reduce hyperalgesia in multiple NP animal models by acting on the dorsal root ganglion. However, a few recent studies have shown that PRF can effectively treat hyperalgesia in pain models by a direct application on injured peripheral nerves. ⋯ The findings suggest that the application of PRF at the impaired SN relieved reduced the CCI-induced NP by through regulating the upregulation of the GDNF expression in the nervous tissues.
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Neuropathic pain affects up to 10% of the general population, but drug treatments recommended for the treatment of neuropathic pain are associated with modest efficacy and/or produce dose-limiting side effects. Hence, neuropathic pain is an unmet medical need. ⋯ One notable exception is the angiotensin II type 2 (AT2) receptor that has clinical validity on the basis of a successful double-blind, randomized, placebo-controlled, clinical trial of EMA401, a highly selective, orally active, peripherally restricted AT2 receptor antagonist in patients with postherpetic neuralgia. In this study, we review research to date on target validation, efficacy, and mode of action of small molecule AT2 receptor antagonists in rodent models of peripheral neuropathic pain and in cultured human sensory neurons, the preclinical pharmacokinetics of these compounds, and the outcome of the above clinical trial.
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Over the last decade, the apparent increase in placebo responses in randomized controlled trials (RCTs) of neuropathic pain have complicated and potentially limited development and availability of new effective pain medication. Placebo analgesia and nocebo hyperalgesia effects are well described in nociceptive and idiopathic pain conditions, but less is known about the magnitude and mechanisms of placebo and nocebo effects in neuropathic pain. In neuropathic pain, placebo treatments have primarily been used as control conditions for active agents under investigation in RCTs and these placebo responses are typically not controlled for the natural history of pain and other confounding factors. ⋯ Large placebo analgesia but no nocebo hyperalgesic effects have been found, and the underlying mechanisms are beginning to be elucidated. Here we review placebo and nocebo effects and the underlying mechanisms in neuropathic pain and compare them with those of nociceptive and idiopathic pain. This allows for a novel discussion on how knowledge of psychological, neurobiological, and genetic factors underlying well-controlled placebo effects may help improve the information that can be obtained from and potentially restore the utility of RCTs.
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Neuropathic pain, ie, pain arising directly from a lesion or disease affecting the somatosensory afferent pathway, manifests with various symptoms, the commonest being ongoing burning pain, electrical shock-like sensations, and dynamic mechanical allodynia. Reliable insights into the mechanisms underlying neuropathic pain symptoms come from diagnostic tests documenting and quantifying somatosensory afferent pathway damage in patients with painful neuropathies. ⋯ Although the mechanisms underlying dynamic mechanical allodynia remain debatable, normally innocuous stimuli might cause pain by activating spared and sensitized nociceptive afferents. Extending the mechanistic approach to neuropathic pain symptoms might advance targeted therapy for the individual patient and improve testing for new drugs.